Fabry Gene Therapy Program Discontinued Following Transient Engraftment Issues


AVRIOBIO announced that it is shifting priorities to focus on their gene therapy programs in Gaucher disease.

AVROBIO is deprioritizing their Fabry disease gene therapy program and stopping recruitment in the phase 1/2 FAB-GT trial (NCT03454893) of AVR-RD-01 following disappointing engraftment data in the 5 most recently treated participants.1

“Previously reported data from 13 patients treated across our three clinical-stage programs have shown durable engraftment out 9 to 54 months. It is the new data from the 5most recently dosed Phase 2 FAB-GT patients that are discordant with these other data and show variable engraftment. In addition, the last 12 months have presented multiple challenging market and regulatory dynamics for our Fabry disease program, which would now be exacerbated by a meaningfully extended development timeline,” Geoff MacKay, president and chief executive officer, AVROBIO, said in a statement.1

“We’re fully aware of the impact this difficult decision has on the patients and families whom we have had the privilege to get to know over the years, but we believe deprioritizing and halting enrollment in our Fabry disease program is the right step forward for AVROBIO and preserves our ability to continue developing therapies with the potential to address urgent unmet needs in the lysosomal disorder community,” MacKay added.1

While durable engraftment was previously observed in the first 4 participants dosed in the study, the 5 most recently dosed patients exhibited variable engraftment. Three participants experienced a return to near-baseline levels of alpha-galactosidase A (AGA) enzyme activity within 3 to 9 months post treatment. These participants also had a reduction in vector copy number (VCN) in whole blood.

WATCH NOW: Challenges With Conducting Clinical Trials in Gaucher Disease: Neil Weinreb, MD

Investigators hypothesize that some participants may have intrinsic resistance to engraftment due to the large degree of heterogeneity in Fabry disease. Enrollment has stopped in the FAB-GT trial and current study participants will be monitored for 15 years.

“Importantly, the drug product specifications for these 5 patients met all release criteria,” MacKay added to the statement.1 “Additionally, these variable engraftment patterns have not been observed to date in data from the other nine Fabry disease patients previously dosed in the Phase 1 trial and under the prior protocol amendments in the FAB-GT trial, or in data from any patients in our other ongoing clinical trials.”

AVROBIO previously presented data at the European Society of Gene & Cell Therapy (ESGCT) meeting, October 19-22, 2021, that showed AVR-RD-01 was well-tolerated in patients with Fabry disease.2 These data were from 9 patients in the FAB-GT trial and 5 patients in the investigator-sponsored phase 1 trial. No patients experienced treatment-related adverse events (AEs) or serious AEs.

AVROBIO also presented safety data from the first patient with Gaucher disease dosed with AVR-RD-02 in the phase 1/2 Guard1 trial (NCT04145037) at ESGCT 2021. The patient has had no serious AEs or AEs related to treatment as of 14 months post-treatment, with a safety date cutoff date of August 31, 2021.

“Powered by our proprietary plato® gene therapy platform, we will focus our efforts on moving value driving clinical-stage programs forward in 2022, with data updates expected for our cystinosis and Gaucher disease type 1 programs, as well as regulatory interactions anticipated across multiple programs in our pipeline,” MacKay said.1

GeneTherapyLive previously spoke with Neil Weinreb, MD, the chair of the International Collaborative Gaucher Group Registry and a member of the AVROBIO safety committee to learn more about gene therapy efforts in Gaucher and Fabry disease. Watch the interview below.

1. AVROBIO reprioritizes pipeline programs. News release. AVROBIO. January 4, 2022. https://investors.avrobio.com/news-releases/news-release-details/avrobio-reprioritizes-pipeline-programs
2. AVROBIO reports new interim safety data across investigational gene therapies for Fabry and Gaucher disease Type 1. News release. AVROBIO. https://www.biospace.com/article/releases/avrobio-reports-new-interim-safety-data-across-investigational-gene-therapies-for-fabry-and-gaucher-disease-type-1/
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